Over one-quarter of all oral antibiotics is prescribed for acute otitis media in the United States. Myringotomy with tympanostomy tube insertion has become the treatment of choice for children with chronic otitis media, with more than two million tubes sold annually in the US. Tympanostomy is the most common pediatric procedure under general anesthesia in the developed world. Chronic post-tympanostomy tube otorrhea is often refractory to treatment and inflicts significant morbidity in the form of hearing loss and long-term middle ear dysfunction. The Co-investigators have confirmed that chronic middle ear infection is a mucosal biofilm disease, and this may explain why otitis media is often difficult to treat with antibiotics. Biofilm on the surface of tympanostomy tubes may be a primary factor in post-tympanostomy otorrhea, and may thus be a source of recurrent infections. Current tympanostomy tubes are ineffective in retarding bacterial attachment and biofilm development. We have discovered that a specific combination of antimicrobial/antibiotic agents incorporated in approved implant host polymers is very effective against bacterial attachment and biofilm development of organisms associated with otitis media. The goal of this study is to develop and test biofilm polymicrobial- resistant implant materials for use as tympanostomy tube implants. The Specific Aims are: 1) to develop polymeric implant materials with selected combinations of antibacterial/antibiotic agents using novel processing methods, and to study their release kinetics, 2) to evaluate bacterial attachment and biofilm development against organisms associated with otitis media, and to define the characteristics of the various antimicrobial/antibiotic combinations to determine MIC values pertaining to planktonic and biofilm inhibition, and 3) to assess the ototoxicity/cytotoxicity of the various antimicrobial/antibiotic combinations. The central innovation of this study is the development of effective implant materials by using special combinations of antimicrobial agents that could specifically retard biofilm development and minimize recurrence of disease, with emphasis on otitis media. [unreadable] [unreadable] [unreadable]